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Quantification of Tryptophan Transport and Metabolism in Lung Tumors Using PET

¹ PET Center, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan; ² Department of Pediatrics, Wayne State University School of Medicine, Detroit, Michigan; ³ Department of Neurology, Wayne State University School of Medicine, Detroit, Michigan; ⁴ The Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan; ⁵ Department of Radiology, Wayne State University School of Medicine, Detroit, Michigan; ⁶ Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan; and ⁷ Department of Medicine, Wayne State University School of Medicine, Detroit, Michigan

Correspondence: For correspondence or reprints contact: Csaba Juhász, PET Center, Children's Hospital of Michigan, 3901 Beaubien Blvd., Detroit, MI 48201. E-mail: juhasz{at}pet.wayne.edu

Abnormal tryptophan metabolism catalyzed by indoleamine 2,3-dioxygenase may play a prominent role in tumor immunoresistance in many tumor types, including lung tumors. The goal of this study was to evaluate the in vivo kinetics of -¹¹C-methyl-L-tryptophan (AMT), a PET tracer for tryptophan metabolism, in human lung tumors. Methods: Tracer transport and metabolic rates were evaluated in 18 lesions of 10 patients using dynamic PET/CT with AMT. The kinetic values were compared between tumors and unaffected lung tissue, tested against a simplified analytic approach requiring no arterial blood sampling, and correlated with standardized uptake values (SUVs) obtained from ¹⁸F-FDG PET/CT scans. Results: Most non–small cell lung cancers (NSCLCs) showed prolonged retention of AMT, but 3 other lesions (2 benign lesions and a rectal cancer metastasis) and unaffected lung tissue showed no such retention. Transport and metabolic rates of AMT were substantially higher in NSCLCs than in the other tumors and unaffected lung tissue. A simplified analytic approach provided an excellent estimate of transport rates but only suboptimal approximation of tryptophan metabolic rates. ¹⁸F-FDG SUVs showed a positive correlation with AMT uptake, suggesting higher tryptophan transport and metabolism in tumors with higher proliferation rates. Conclusion: Prolonged retention of AMT in NSCLCs suggests high metabolic rates of tryptophan in these tumors. AMT PET/CT may be a clinically useful molecular imaging method for personalized cancer treatment by identifying and monitoring patients who have increased tumor tryptophan metabolism and are potentially sensitive to immunopharmacotherapy with indoleamine 2,3-dioxygenase inhibitors.

Key Words: lung tumors • positron emission tomography • tryptophan • metabolism • 2-deoxy-2-[¹⁸F]fluoro-D-glucose

COPYRIGHT © 2009 by the Society of Nuclear Medicine, Inc.

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